3-Hydroxypyridine → 3-(1H-Benzimidazol-2-yl)-5-(3-pyridyloxy)pyrazin-2-amine

Participants

Reaction Steps

3-(1H-Benzimidazol-2-yl)-5-bromo-pyrazin-2-amine (100 mg, 0.3447 mmol), dicesium carbonate (366 mg, 1.034 mmol), copper (2.2 mg, 0.034447 mmol) and pyridin-3-ol (327.8 mg, 3.447 mmol) in DMF (2 mL) were heated at 130° C. under microwave conditions for 1 hour. The reaction mixture was filtered through a pad of silica eluting with 90 to 100% EtOAc/Petroleum Ether and the relevant fractions concentrated in vacuo. The resiude was redissolved in EtOAc and washed with saturated aqueous NaHCO3 (×2) and brine (×1), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 mM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound as a yellow solid (12 mg, 11% Yield). 1H NMR (400.0 MHz, CDCl3) δ 7.33-7.38 (2H, m), 7.77-7.8 (2H, m), 7.82-7.88 (1H, m), 8.05-8.1 (1H, m), 8.15 (1H, s), 8.8-8.55 (1H, m) and 10.2 (1H, s) ppm; MS (ES+) 305.

Provenance & Evidence